An induced-fit model for asymmetric organocatalytic reactions: a case study of the activation of olefins via chiral Brønsted acid catalysts.

We elucidate the stereo-controlling factors of the asymmetric intramolecular hydroalkoxylation of terminal olefins catalyzed by bulky Brønsted acids [ Science 2018 , 359 (6383), 1501-1505] using high-level electronic structure methods. The catalyst-substrate interaction is described using a dispersion-driven induced-fit model, in which the conformational changes of the catalyst and of the substrate in the transition states are governed to a large extent by London dispersion forces. The distortion energy of the catalyst is dominated by the change in the intramolecular dispersion interactions, while intermolecular catalyst-substrate dispersion interactions are the major stabilizing contribution in the transition state. This model provides a new general framework in which to discuss the stereoselectivity of transformations catalyzed by such confined organocatalysts.